Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.

Background: Melatonin has been shown to be neuroprotective in different animal models of neonatal hypoxic-ischemic brain injury. However, its exact molecular mechanism of action remains unknown. Our aim was to prove melatonin's short- and long-term neuroprotection and investigate its role on the AMPK (AMP-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway following neonatal hypoxic-ischemic brain injury.

Transcatheter dilation and stenting of the modified blalock-taussig shunt in cyanotic heart diseases: points to consider. A single-center experience.

Background: Our study focuses on the technique and results of interventional dilation and stenting of the modified Blalock-Taussig shunt (MBTS) performed in our center, providing a comprehensive review of our practice over the past 4 years.

Methods: 42 catheter interventions on MBTS performed on 32 patients between January 2020 and May 2024 included 11 balloon dilatations and 31 stenting procedures. They were analyzed retrospectively.

Applications of Point-of-Care-Ultrasound in Neonatology: A Systematic Review of the Literature.

Point-of-care ultrasound (POCUS) integration into neonatology offers transformative potential for diagnostics and treatment, enhancing immediacy and precision of clinical decision-making in this vulnerable patient population. This systematic review aims to synthesize evidence on POCUS applications, benefits, challenges, and educational strategies in neonatology. Literature search was conducted using SPIDER scheme keywords and MeSH terms related to POCUS and neonatology.

Microbiological Screening of Donor Human Milk.

Mother's own milk is recognized as the optimal feeding not only for term but also for preterm infants. In addition to risk reduction for sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity in the early infancy, feeding preterm infants with mother's own milk is also associated with a better neurodevelopmental outcome; lower rates of otitis media, gastroenteritis, and respiratory infections; and a reduced risk of cardiovascular disease, obesity, and diabetes later in life. Donor human milk is the best alternative if mother's own milk is not available or with short supply.

Correlation of Different MRI Scoring Systems with Long-Term Cognitive Outcome in Cooled Asphyxiated Newborns.

(1) Background: Cerebral MRI plays a significant role in assessing the extent of brain injury in neonates with neonatal encephalopathy after perinatal asphyxia. Over the last decades, several MRI scoring systems were developed to enhance the predictive accuracy of MRI. The aim of this study was to validate the correlation of four established MRI scoring systems with cognitive long-term outcomes in cooled asphyxiated newborns.

Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial.

Intrapartum hypoxia-ischemia leading to neonatal encephalopathy (NE) results in significant neonatal mortality and morbidity worldwide, with > 85% of cases occurring in low- and middle-income countries (LMIC). Therapeutic hypothermia (HT) is currently the only available safe and effective treatment of HIE in high-income countries (HIC); however, it has shown limited safety or efficacy in LMIC. Therefore, other therapies are urgently required.

Restraint stress during neonatal hypoxia-ischemia alters brain injury following normothermia and hypothermia.

Rodent models of neonatal hypoxic-ischemic (HI) injury require a subset of animals to be immobilized for continuous temperature monitoring during the insult and subsequent treatment. Restrained animals are discarded from the analysis due to the effect of restraint on the brain injury as first demonstrated by Thoresen et al 1996. However, the effects of restraint on responses to hypothermic (HT) post-insult therapy are not well described.

Temporal Characterization of Microglia-Associated Pro- and Anti-Inflammatory Genes in a Neonatal Inflammation-Sensitized Hypoxic-Ischemic Brain Injury Model.

Hypoxic-ischemic encephalopathy (HIE) mainly affects preterm and term newborns, leading to a high risk of brain damage. Coexisting infection/inflammation and birth asphyxia are key factors associated with intracerebral increase of proinflammatory cytokines linked to HIE. Microglia are key mediators of inflammation during perinatal brain injury, characterized by their phenotypic plasticity, which may facilitate their participation in both the progression and resolution of injury-induced inflammation.

Fluid Supply and Feeding Practices in Cooled Asphyxiated Newborns.

Therapeutic hypothermia (TH) for 72 h is the standard treatment to reduce neurological deficits in term newborns with hypoxic-ischemic encephalopathy. There is a large variability regarding nutritional supply during TH treatment in asphyxiated newborns. We performed a retrospective multicentre study in four level I (highest level of care in Germany) NICUs, including 135 asphyxiated term newborns undergoing TH.

Inflammasome-induced extracellular vesicles harbour distinct RNA signatures and alter bystander macrophage responses.

Infectious organisms and damage of cells can activate inflammasomes, which mediate tissue inflammation and adaptive immunity. These mechanisms evolved to curb the spread of microbes and to induce repair of the damaged tissue. Chronic activation of inflammasomes, however, contributes to non-resolving inflammatory responses that lead to immuno-pathologies.

Innate immunity, inflammation activation and heat-shock protein in COVID-19 pathogenesis.

SARS-CoV-2-induced COVID-19 is a serious pandemic of the 21st century, which has caused a devastating loss of lives and a global economic catastrophe. A successful vaccine against SARS-CoV-2 has suffered a delay due to lack of substantial knowledge about its mechanisms of action. Understanding the innate immune system against SARS-CoV-2 and the role of heat shock proteins' (HSP) inhibiting and resolution of inflammatory pathways may provide information to the low SARS-CoV-2 mortality rates in Africa.

Therapies for neonatal encephalopathy: Targeting the latent, secondary and tertiary phases of evolving brain injury.

In term and near-term neonates with neonatal encephalopathy, therapeutic hypothermia protocols are well established. The current focus is on how to improve outcomes further and the challenge is to find safe and complementary therapies that confer additional protection, regeneration or repair in addition to cooling. Following hypoxia-ischemia, brain injury evolves over three main phases (latent, secondary and tertiary), each with a different brain energy, perfusion, neurochemical and inflammatory milieu.

Unanswered questions regarding therapeutic hypothermia for neonates with neonatal encephalopathy.

Therapeutic hypothermia (TH) is now well established to improve intact survival after neonatal encephalopathy (NE). However, many questions could not be addressed by the randomized controlled trials. Should late preterm newborns with NE be cooled? Is cooling beneficial for mild NE? Is the current therapeutic time window optimal, or could it be shortened or prolonged? Will either milder or deeper hypothermia be effective? Does infection/inflammation exposure in the perinatal period in combination with NE offer potentially beneficial preconditioning or might it obviate hypothermic neuroprotection? In the present review, we dissect the evidence, for whom, when and how can TH best be delivered, and highlight areas that need further research.

Mechanical Ventilation, Partial Pressure of Carbon Dioxide, Increased Fraction of Inspired Oxygen and the Increased Risk for Adverse Short-Term Outcomes in Cooled Asphyxiated Newborns.

Neonates treated with therapeutic hypothermia (TH) following perinatal asphyxia (PA) suffer a considerable rate of disability and mortality. Several risk factors associated with adverse outcomes have been identified. Mechanical ventilation might increase the risk for hyperoxia and hypocapnia in cooled newborns.

Association of Routinely Measured Proinflammatory Biomarkers With Abnormal MRI Findings in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.

The neuroprotective treatment effect of therapeutic hypothermia (TH) following perinatal asphyxia may be negatively influenced by neonatal sepsis and concomitant inflammation. We aimed to correlate routinely used blood biomarkers for perinatal sepsis in cooled asphyxiated newborns with MRI findings. Perinatal data was retrospectively collected from 67 cooled asphyxiated newborns.

Perinatal Infection: A Major Contributor to Efficacy of Cooling in Newborns Following Birth Asphyxia.

Neonatal encephalopathy (NE) is a global burden, as more than 90% of NE occurs in low- and middle-income countries (LMICs). Perinatal infection seems to limit the neuroprotective efficacy of therapeutic hypothermia. Efforts made to use therapeutic hypothermia in LMICs treating NE has led to increased neonatal mortality rates.

Involvement of CXCL1/CXCR2 During Microglia Activation Following Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats.

Microglia are key mediators of inflammation during perinatal brain injury. As shown experimentally after inflammation-sensitized hypoxic ischemic (HI) brain injury, microglia are activated into a pro-inflammatory status 24 h after HI involving the NLRP3 inflammasome pathway. The chemokine (C-X-C motif) ligand 1 (CXCL1), and its cognate receptor, CXCR2, have been shown to be involved in NLRP3 activation, although their specific role during perinatal brain injury remains unclear.

Variability and sex-dependence of hypothermic neuroprotection in a rat model of neonatal hypoxic-ischaemic brain injury: a single laboratory meta-analysis.

Therapeutic hypothermia (HT) is standard care for term infants with hypoxic-ischaemic (HI) encephalopathy. However, the efficacy of HT in preclinical models, such as the Vannucci model of unilateral HI in the newborn rat, is often greater than that reported from clinical trials. Here, we report a meta-analysis of data from every experiment in a single laboratory, including pilot data, examining the effect of HT in the Vannucci model.

Effects of altered photoperiod due to COVID-19 lockdown on pregnant women and their fetuses.

Maternal circadian rhythms provide highly important input into the entrainment and programming of fetal and newborn circadian rhythms. The light-dark cycle is an important regulator of the internal biological clock. Even though pregnant women spend a greater part of the day at home during the latter stages of pregnancy, natural light exposure is crucial for the fetus.

A novel thermoregulatory role for PDE10A in mouse and human adipocytes.

Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the novel radioligand [(18)F]-AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice.

Cre-dependent DNA recombination activates a STING-dependent innate immune response.

Gene-recombinase technologies, such as Cre/loxP-mediated DNA recombination, are important tools in the study of gene function, but have potential side effects due to damaging activity on DNA. Here we show that DNA recombination by Cre instigates a robust antiviral response in mammalian cells, independent of legitimate loxP recombination. This is due to the recruitment of the cytosolic DNA sensor STING, concurrent with Cre-dependent DNA damage and the accumulation of cytoplasmic DNA.

Familial tetrasomy 4q35.2 associated with congenital diaphragmatic hernia and unilateral renal agenesis: a case report.

Background: Previous reports of chromosomal aberrations in different forms of congenital diaphragmatic hernia have been described as comprising aneuploidies (for example, trisomy 21), microdeletions, and duplications (for example, monosomy 15q24, 22q11.2).

Case Presentation: We describe the first association of a de novo partial tetrasomy 4q35.